The research proposed will use acetylcholine receptor from Electrophorus electricus electric organ extensively purified by affinity chromatography on an adsorbent of cobra neurotoxin according to a method I have devised. This research has two principal objectives. The first objective is to determine the molecular mechanism by which reversible binding of the neurotransmitter acetylcholine causes the receptor to increase the cation permeability of the postsynaptic membrane. This involves study of (1) the purity of the receptor preparation, (2) the polypeptide chain composition of the receptor, and (3) the incorporation of purified receptor into artificial lipid bilayer membranes in a functional form. Promising results have already been obtained in all three areas. The second objective is to determine the nature of an experimental autoimmune disease of rabbits caused by immunization with this purified acetylcholine receptor. Immunized rabbits exhibit peripheral flaccid paralysis and fatiguing of their electromyograph response at high frequencies, both of which symptoms are dramatically relieved by injection of anti-esterase drugs. Their behavior in this respect is identical to that of human victims of myasthenia gravis. Thus, expanded study of the sera of paralyzed rabbits and myasthenia gravis patients may explain the etiology of disease symptoms and provide an animal model for myasthenia gravis.